HSPA4

protein-coding

heat shock protein family A (Hsp70) member 4, the group of Heat shock 70kDa proteins

Gene summary

Predicted to enable adenyl-nucleotide exchange factor activity. Involved in chaperone-mediated protein complex assembly and protein import into mitochondrial matrix. Located in cytosol and extracellular exosome. Implicated in Chagas disease. Biomarker of chronic obstructive pulmonary disease; rheumatoid arthritis; type 2 diabetes mellitus; and ulcerative colitis. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_002154.4

Inheritance

—

ClinVar variants

U:94B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr5:133,052,013-133,106,449

External References & Databases

Ensembl (ENSG00000170606)

Transcript & Mutation Effects

hg38 • Region Span ~54.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HSPA4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 79

not providedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002154.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	2 clinvar	4 clinvar	8
missense			83 clinvar	3 clinvar	1 clinvar	87
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	94	5	5	104

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002154.4	RefSeq	NP_002145.3	19	MANE Select
ENST00000304858.7	Ensembl	ENSP00000302961.2	19	MANE Select
ENST00000870715.1	Ensembl	ENSP00000540774.1	19	Standard
ENST00000870715.2	Ensembl	ENSP00000540774.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Antigen processing and presentation - Homo sapiens (human)
Tight junction - Homo sapiens (human)
Glucocorticoid Pathway (Peripheral Tissue), Pharmacodynamics
Parkin-Ubiquitin Proteasomal System pathway
Regulation of HSF1-mediated heat shock response

Biological Process

response to unfolded protein
protein insertion into mitochondrial outer membrane
chaperone-mediated protein complex assembly

Molecular Function

protein binding
ATP binding

Cellular Component

nucleus
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304858
Coding exons: 19
Length: 54488
Individuals with no LoFs: 125631
Homozygous LoFs: 0
Heterozygous LoFs: 116
Defined: 125747
p: 0.000461

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.06	311	431	0.721	0.0000207	5549
Missense (PolyPhen)		106	193.41	0.54806		2477
Synonymous	-0.486	156	148	1.05	0.00000711	1505
Loss of Function	5.66	6	48.5	0.124	0.00000284	583

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00018	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.0027	0.0012	notable
East Asian	0.00061	0.00033	rare
Finnish	0.0010	0.00051	notable
European (Non-Finnish)	0.0014	0.00069	notable
South Asian	0.000041	0.000033	rare
Other	0.0018	0.00081	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.952

Intolerance Scores

LoFtool: 0.407
RVIS EVS: -0.15
RVIS percentile EVS: 42.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.909

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium